Support is requested to develop a program of research to study the metabolism of arachidonic acid within small intraparenchymal blood vessels (the major resistance vessels) and larger vesseLs isolated from bovine brains as well as from the brains of spontaneously hypertensive rats (SH rats), and from its genetic normotensive relative, the Kyoto-Wistar rat. We will examine the extent to which vasoactive molecules and other compounds (e.g., cateCholamineS, indoleamines, histamine, angiotensin II, bradykinin, complement fragments C3A and C5B (as well as several agonists and antagonists of the above) modify the metabolism of arachidonic acid in organ culture. Prostaglandins E2, D2, F2 alpha, thromboxane A2, prostacyclin, and 12-HETE will be measured by radioimmunoassays already developed in our laboratories. Vessels isolated form normal rats and from rats with varying degrees of hypertension and at various stages of its development (e.g., before the onset of hypertension) will be studied. We will compare these results with those obtained using brain capillaries, and segments of larger cerebral arteries prepared from normotensive and SH rats. The effects of antihypertensive treatments on the metabolism of arachidonic acid will also be assessed in vivo and in vitro. The extent to which denervating large and small blood vessels (by lesions of superior cervical ganglia, locus coeruleus and midbrain raphe nuclei) alters the metabolism of arachidonic acid will be determined. By so doing, we will: a) examine the metabolism of arachidonic acid and prostaglandins within blood vessels of an organ (brain) that is susceptible to the complications of hypertension (thrombosis and hemorrhage); b) compare the metabolism of arachidonic acid in cerebral blood vessels of differing size (capillaries, arterioles, arteries) during the development of hypertension, c) determine to what extent the autonomic nervous system modifies vascular metabolism of arachidonic acid d) examine the possibility that AA metabolism may be altered prior to, or during the initiation and/or maintenance of hypertension in the spontaneously hypertensive rat.